2,6,10-Trimethyl-10-hydroxy-dodeca-2,6,11-trien-al as a perfuming agent

ABSTRACT

A perfuming or odour-modifying agent consisting essentially of or comprising 2,6,10-trimethyl-10-hydroxy-dodeca-2,6,11-trien-1al. A process for the manufacture of 2,6,10-trimethyl-10-hydroxydodeca-2,6,11-trien-1-al.

United States Patent [191 Demole [54] 2,6,l0-TRIMETHYL-10-HYDROXY- DODECA-2,6,ll-TRIEN-l-AL AS A PERFUMING AGENT [75] Inventor: Edouard P. Demole, Coppet, Switzerland [73] Assignee: Firmenich S.A., Geneva,

Switzerland 22 Filed: June 27, 1974 211 App]. No.: 483,553

[30] Foreign Application Priority Data June 29, 1973 Switzerland 9495/73 521 US. Cl 252/522; 260/602 [51] Int. Cl. CllB 9/00 Oct. 28, 1975 [58] Field of Search 252/522 [56] References Cited FOREIGN PATENTS OR APPLICATIONS 2,143,992 9/197] Germany 252/522 Primary Examiner-Veronica OKeefe Attorney, Agent, or Firm-Pennie & Edmonds 4 Claims, No Drawings 2,6,l-TRIMETHYL-IO-HYDROXY-DODECA- 2,6,11-TRlEN-AL AS A PERFUMING AGENT BACKGROUND OF THE INVENTION -CH0 I i! i fl CH2=CH-- -CH2CH. ,CH= -CH2CH2--CH OH is a known compound (cf. West German patent application DOS 2,143,992 laid open to public inspection) which is used as an intermediate in the synthesis of asinensal and B-sinensal, the latter being natural constituents of the mandarin and tangerine flavour.

The structure of hydroxysinensal being very similar to that of aand B-sinensal, it was reasonable to expect that hydroxysinensal would also have a similar odour, i.e., would develop a mandarinor tangerine-like odour or at least an odour reminiscent of mandarin or tangerine, as it is suggested in the above-mentioned West German patent application. However, I could not confirm this. To my surprise I found that the odour of hydroxysinensal is quite different from that of the sinensals. Its odour is not fruity but floral and reminiscent of the fragrance developed by the lily of the valley and is very tenacious. Furthermore, the odour of aldehyde I is free from the citrus note which characterizes the sinensals. Hydroxysinensal as such already constitutes a complete perfume. It can be used as a base in the preparation of perfumes or as a modifier to be added to perfume compositions and permits to obtain very interesting floral olfactive effects.

SUMMARY OF THE INVENTION by using 2,6,10-trimethyl-l0-hydroxy-dodeca-2,6, 1 1- trien-l-al as an odoriferous ingredient or additive.

Another object of the invention is to provide odoriferous compositions, such as perfumes, perfumed products and essential oils, having added thereto an odourmodifying amount of 2,6, lO-trimethyl-lO-hydroxydodeca-2,6,I l-trien- 1 -al.

The term perfumed products includes e.g. soaps, cosmetic products, detergents and the like.

DETAILED DESCRIPTION Hydroxysinensal can be used alone, i.e., without being admixed to other odoriferous substances, as a fragrance. Preferably, it is used in diluted form. The diluents or solvents usually used in perfumery, e.g. ethyl alcohol or diethyl phthalate, can be used for this purpose. Hydroxysinensal as such can be used for perfuming soaps, cosmetic products, detergents and the like.

When hydroxysinensal is used as perfume ingredient together with other odoriferous substances in perfume compositions, its concentration can vary within wide limits, e.g. between 2 and 20 based on the total weight of a perfume composition. However, the concentration of hydroxysinensal can exceed 20 and reach for example or more when special olfactive effects are to be obtained. As a rule, hydroxysinensal imparts strong floral odour notes to perfume compositions and enhances as well as harmonizes the floral odour component of the perfumes to which it is added.

According to the invention 2,6,IO-trimethyl-10- hydroxy-dodeca-2,6,I l-trien-I-al is prepared by reacting nerolidol (II) with N-bromosuccinimide in order to obtain 2-methyl-2-vinyl-5-( 1,5-dimethyl- 1 -bromo-hex- 4-en-1-yl)-tetrahydrofuran (III), converting the latter to its mono-ozonide and reducing the ozonide in order to obtain 2-methy1-2-vinyl-5-( 1-methyl-I-bromo-3-formyl-prop-1-y1)-tetrahydrofuran (IV), acetalizing the latter, reacting the resulting acetal (V) with a reducing metal in a substantially anhydrous medium and subsequently with water, hydrolysing the resulting acetal of 4,8-dimethyl-8-hydroxy-deca-4,9-dien- 1 -al (VI) in order to obtain 4,8-dimethyl-8-hydroxy-deca-4,9-dien- I-al (VII), and subjecting the latter to a Wittig reaction with 1-formy1-ethylidenetriphenyl-phosphorane in order to obtain 2,6,10-trimethyl-l0-hydroxy-dodeca- 2,6,1l-trien-l-al (I).

The above-defined process can be illustrated as fol- .lows:

I ozonisution 2 reduction lacetalisation ucetalisation l) reducing metal 1) H O hydrolysis R alkyl group or 2R alkylene group As a starting compound or ()-nerolidol can be used in the form of its cisor trans-isomer or of mixtures of these isomers.

The reaction between nerolidol and N-bromosuccinimide is conveniently carried out at temperatures neighbouring C, preferably at 1820C. The reaction time can vary between about 27 and 170 hours. As to the other reaction conditions, the method described in Helv. Chim. Acta 54, 461 (1971) can be applied.

The ozonolysis of compound III can be carried out by known methods, e.g. at 70C in methanol. As a reducing agent for the reduction of the ozonide e.g. methyl sulphide, triphenylphosphine or trimethylphosphite can be used.

The acetalisation of aldehyde VI can be carried out by usual methods. The acetal can be either cyclic of non-cyclic.

The dehydrobromination of acetal V can be carried out by means of metallic sodium in a substantially anhydrous medium, e.g. in tetrahydrofuran, or by means of zinc powder in acetic acid.

The Wittig reagent with which aldehyde VII is reacted can be obtained by the method described in I-Ielv. Chim. Acta 50, 2445 (1967).

2,6, 10-Trimethyl-10-hydroxy dodeca-2,6,l l-trienl-al can theoretically exist in the form of four configuration isomers, viz. the 2cis,6cis, 2cis,6trans, 2trans,6- trans and 2trans,6cis isomers. The isomers having cisconfiguration in position 2 are, however, not stable. In the process of the invention mixtures of the 2trans,6- trans and 2trans,6cis isomers are formed as a rule. The ratio in which the two isomers are formed varies within VII certain limits and can, e.g., be about 30 of the 2trans,6cis isomer to of the 2trans,6trans isomer. Since the two isomers have similar olfactive properties, it is not necessary to separate them before they are used as perfuming agents. The mixture of isomers as obtained by the process of the invention can be used directly for perfuming purposes.

It is obvious that instead of 2,6,10-trimethy1-l0- hydroxy-dodeca-2,6,1 l-trien-l-al its precursors, e.g. its acetals which will yield the aldehyde under acid conditions, can also be used.

The invention is further illustrated by the following Examples wherein temperatures are given in degrees Centigrade.

EXAMPLE 1 A perfume base was prepared by mixing the following ingredients:

Ingredients Parts by weight 1,1-Dimethyl-4-acetyl-6- Dicthyl phthalatc IUU -continued lngredients Parts by weight Total 1 000 in diethyl phthalate This perfume base developed an unspecific floral odour. By adding 100 parts by weight of hydroxysinensal to 900 parts of the perfume base a perfume composition developing a strong lily of the valley-like odour was obtained. This perfume was particularly suitable for perfuming facial creams.

For the purpose of comparison, parts by weight of a-sinensal were added to 990 parts of the same perfume base. The resulting composition developed an odour which was characterized by a strong citrus note. The lily of the valley-like odour had completely disappeared.

EXAMPLE 2 A perfume base was prepared by mixing the following ingredients: 8n

*in dielhyl phthalate This perfume base developed a warm and somewhat amber-like odour. 100 parts by weight of hydroxysi nensal were added to the perfume base. The resulting perfume composition developed a substantially improved and enhanced fragrance. Whereas in the perfume base the floral notes were somewhat overshadowed by the amber note, the floral notes fully developed from the perfume composition containing hydroxysinensal. Furthermore, this perfume developed a particularly elegant fragrance.

Hydroxysinensal which has a discrete but very tenacious floral note enhances and harrnonizes the floral notes in perfumes and is, therefore, a very valuable perfume ingredient.

When the same amount, or even only 1 7c, of asinensal is added to the perfume base instead of hydroxysinensal, the olfactive properties of the perfume base are totally changed. A strong fruity odour overshadows entirely all the other odour notes of the perfume base.

EXAMPLE 3 A mixture of 44.4 g (0.2 mole) of (i)-nerolidol (II, mixture of cis and trans isomers), 37.4 g (0.21 mole) of N-bromosuccinimide and 500 ml of CCL, was stirred for 6 days at 1820. One volume of petroleum ether (boiling range 3050) was added to the reaction mixture, and the precipitated solid was filtered off. 0.5 g of sodium acetate was added to the filtrate which was then concentrated at 10 mm Hg. There were thus obtained 63 g of 2-methyl-2-vinyl-5-( 1,5-dimethyl- 1 -bromo-hex- 4-en-l-yl)-tetrahydrofuran (II) as a residue. This residue was taken up in 630 ml of methanol, and the solution was treated at with a stream of ozone-containing oxygen for 3 /2 hours (corresponding to 0.2 mole of 0 The solution was maintained at 70 and treated with a vigorous stream of nitrogen, and 30 ml of methyl sulphide were added. The reaction mixture was allowed to warm up to 20 within 12 hours under nitrogen. The reaction mixture was concentrated at 10 mm Hg. The residue was taken up in ether (two separating funnels). The ether solution was washed three times with water and then with brine, subsequently dried over magnesium sulphate and concentrated. A residue consisting of 2-methyl-2-vi ny1-5-( l-methyl- 1-bromo-3-formyl-prop-l-yl)-tetrahydrofuran (III) was obtained.

The residue was refluxed in a mixture of 250 ml of benzene, 16.1 g (0.26 mole) of ethyleneglycol and mg of p-toluenesulphonic acid (using a Dean-Stark separator). The heating was continued for 2 hours after the formation of water had stopped. Then, 100 ml of benzene were slowly removed by distillation. The remaining solution was washed with 10 sodium carbonate solution (3 times) and with brine (twice). After removal of the solvent at 10 mm Hg the ethylene acetal V of aldehyde IV was obtained asa residue.

The residue was taken up in ml of anhydrous tetrahydrofuran, and the resulting solution was added to a stirred suspension of 9.65 g (0.42 mole) of powdered soda in 500 ml of the same solvent. After stirring for a few hours at 20. the temperature of the reaction mixture spontaneously rose. The reaction mixture was maintained at 40for 6 hours (first by cooling and then by heating). A further quantity of 4.8 g (0.2 mole) of powdered sodium suspended in 100 ml of tetrahydrofuran was added, and the reaction mixture was stirred for 15 hours at 40. After cooling the liquid phase was carefully separated from the agglomerated sodium. A small quantity of ethanol was added to the liquid phase, and then the solvent was removed under reduced pressure. The residue was taken up in water. The resulting solution was extracted with ether (twice). The ether ex tract was washed with water (5 times) and then rapidly distilled at 0.001 mm Hg. The distillate was again fractionated in a Vigreux column (30 cm; equipped with an adjustable reflux head). 21.4 g (44.6 7c based on nerolidol) of the ethylene acetal of 4,8-dimethy1-8 hydroxydeca-4,9-dien-l-al (V1), b.p. 97105/0.00l mm Hg, were thus isolated. This product consisted of a mixture of the cis and trans isomers which were separated by distillation in a spinning band column. The cis isomer is more volatile than the trans isomer.

Acetal VI cis: df" 0.9977; 1.4816;

1R(fi1m): 920, 990, 1410, 1640, 3100 (CH=CH.

1140 (C-O), 3470 cm (OH); MS: M almost invisible at m/e 240. base peak at m/e NMR: 8= 1.25 (3H, s), 1.69 (3H, s broad), 1.30-2.30 (9H, m), 3.87 (4H, m), 4.80 (1H, t, J 4.5 cps), 4.88-5.35 (3H, m), 5.92 (1H, d/d, J =17, J cps) ppm.

Calculated for C H ,O C69.96, H-l0.07

Found: C69.95, Hl0.2l

Acetal V1 trans: (1 0.9975; 11,, 1.4833;

IR (film): 920, 1410, 1640, 3100 (CH=CH- 1140 (C-O), 3470 cm" (OH);

MS: M almost invisible at m/e 240, base peak at m/e NMR: 6 1.25 (3H, s), 1.62 (3H, s broad), 1.30-2.30 (9H, m), 3.85 (4H. m), 4.80 (1H, t, J 4.5 cps), 4.88-5.35 (3H, m), 5.92 (1H, d/d, J =17, J 10 cps) ppm.

A solution of 4.85 g (20 mmoles) of one of the acetals VI in a mixture of 120 ml dioxan and 45 ml of 0.02 N sulphuric acid was refluxed for 3 hours. The solution was allowed to cool to 20, and 10 ml of 5 aqueous sodium bicarbonate were added thereto. The reaction mixture was stirred for minutes. After removal of the dioxan the residue was taken up in ether. The solution was washed with 5 aqueous sodium bicarbonate (once), water (three times) and brine (once). After the usual treatment and distillation 2.84 g (72 of a mixture of cis and trans 4,8-dimethyl-8-hydroxy-deca-4,9- dien- 1 als were obtained.

Aldehyde V11 cis: b.p. 83-85/0.001 Torr; 11

[R (film): 915, 990, 1410, 1635, 3080 (CH=CH 1105 (C-O), 1715 (C=O), 2720, 2850 (CHO), 3450 cm (OH);

MS: M invisible, M-18 at m/e 178, base peak at m/e NMR: 8= 1.23 (3H, s), 1.66 (3H, s broad), 2.37 (3H, m narrow), 1.30-2.50 (5H, m), 2.60 (1H, s, OH), 4.80-5.30 (3H, m), 5.88 (1H, d/d, J =17, J =10 cps), 9.71 (1H, t, J about 1.5 cps) ppm.

Aldehyde V11 trans: b.p. 9395/0.001 Torr; (1

[R (film): 915; 990, 1410, 1635, 3080 (-CH=CH 1110 (CO), 1715 (C=O), 2720, 2850 (CHO). 3450 cm (OH);

MS: M invisible, M-18 at m/e 178, base peak at m/e NMR: 8 1.26 (3H, s), 1.60 (3H, s broad), 1.30-2.60 (9H, m), 4.80-5.30 (3H, m), 5.83 (1H, d/d, J =17, J =10 cps), 9.32 1H. t. J =about 1.5 cps) ppm.

Calculated for C H O C73.43, Hl0.27 7:.

Found: C-73.40, H-10.41 7a.

A mixture of 1.147 g (5.83 mmoles) of cis aldehyde V11, 1.95 g (6.14 mmoles) of l-formyl-ethylidene-triphenylphosphorane and 12 ml of anhydrous benzene was refluxed for 50 hours in a nitrogen atmosphere. The solvent was removed at reduced pressure, and the residue was taken up in a 1:1 mixture of ether and petroleum ether (boiling range -50). After filtration of the solution the filtrate was concentrated. The residue was distilled at 0.001 mm Hg. b.p. 112. 1.069 g (77.4 7r) of 2,6,l0-trimethyl-10-hydroxy-dodeca- 2trans,6cis,10-trien-1-al (l) were obtained. This product had the following physical properties:

8 (1 0.9577; n 1.5009; IR (film): 915, 990, 1400, 3080 (CH=CH 1100 2700, 2850 (CHO), 3450 cm (OH);

MS: M invisible, M-18 at m/e 218, intense fragments at m/e 43 (base peak), 55, 71, 93; NMR: 8= 1.26 (3H, s), 1.70 (6H, s broad), 2.62 (1H, s, OH), 1.30-2.80 (8H, m), 4.80-5.40 (3H, m), 5.86 (1H, d/d, J =17, J =10 cps),6.43 (1H, t, J

a 6 cps 10.33 (1H, 5) ppm.

This latter signal (proton of CHO) appeared at 8 9.27 when the measurement was made in CCl 3.65 g 16.5 mmoles) of trans aldehyde V11 were reacted in the manner described above with 5.53 g 17.4 mmoles) of 1formyl-ethylidene-triphenyl-phosphorane in 35 ml of anhydrous benzene. 3.6 g of a crude product boiling at 115-122/0.001 mm Hg were obtained. This product was purified by chromatography on a column of g of silicagel (Mallinckrodt, 100 mesh). Elution with a 7:3 mixture of benzene and ether yielded 2.632 g (67.5 of 2,6,lO-trimethyl-10- hydroxy-dodeca-2trans,6trans, l l-trien- 1 al. This compound had the following physical properties:

B.p. 118120/0.001 mm Hg; d 0.9557; m,

1.5009; [R (film): 915, 990, 1400, 3080 (CH=CH 1635,

2700, 2850 (-CHO), 3450 cm (OH);

MS: M invisible, M-18 at m/e 218, intense fragments at m/e 43 (base peak), 55, 93;

NMR18=1.25(3H, s), 1.62 (3H, s broad), 1.71 (3H,

s broad), 1.30-2.70 (8H, m), 2.50 (1H, s. OH),

4.86-5.33 (3H, m), 5.91 (1H, d/d, J =17, J' =10 cps), 6.45 (1H, t, J 6 cps), 9.60 (1H, 5) ppm. This latter signal (proton of CHO) appeared at 5 9.27 when the measurement was made in CC1 I claim:

1. :A process for improving, enhancing or otherwise modifying the odoriferous properties of perfumes, perfumed products and natural or synthetic essential-oils which comprises adding thereto an odour-modifying amount of 2,6, l O-trimethyl- 1 O-hydroxy-dodeca- 2,6,1 l-trien-l-al.

2. An odoriferous composition selected from the class consisting of perfumes, perfumed products and natural or artificial essential oils having added thereto an odour-modifying amount of 2,6,l0-trimethyl-l0- hydroxy-dodeca-2.6. 1 l trien- 1 al.

3. A perfume composition which comprises as one of its odoriferous ingredients 2,6,10-trimethyl-l0- hydroxy-dodeca-2,6, 1 1 -trien-l-a1.

4. A perfume composition which comprises 2,6,10- trimethyll 0-hydroxy-dodeca-2,6,l l-trien- 1 al and a diluent or a carrier.

UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT NO. 1 3,915,901

DATED 1 October 28, 1975 |Nv T0R(5) Edouard P. Demole It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

IN THE TITLE OF THE INVENTION:

"TRIEN-AL' Should read TRIENlAL-.

Column 3, line 52, "of" should read -or.

Column 5, line 22, "8n" should be .deleted.

Signed and Scaled this ninth Day Of March1976 [SEAL] Arrest:

RUTH C. MASON C. MARSHALL DANN Arresting Officer Commissioner ofParenrs and Trademarks 

1. A PROCESS FOR IMPROVING, ENHANCING OR OTHERWISE MODIFYING THE ODORIFEROUS PROPERTIES OF PERFUMES, PERFUMED PRODUCTS AND NATURAL OR SYNTHETIC ESSENTIAL OILS WHICH COMPRISES ADDING THERETO AN ODOUR-MODIFYING AMOUNT OF 2,6,10-TRIMETHYL-10-HYDROXY-DODECA-2,6,11-TRIEN-1-AL.
 2. An odoriferous composition selected from the class consisting of perfumes, perfumed products and natural or artificial essential oils having added thereto an odour-modifying amount of 2,6,10-trimethyl-10-hydroxy-dodeca-2,6,11-trien-1-al.
 3. A perfume composition which comprises as one of its odoriferous ingredients 2,6,10-trimethyl-10-hydroxy-dodeca-2,6, 11-trien-1-al.
 4. A perfume composition which comprises 2,6,10-trimethyl-10-hydroxy-dodeca-2,6,11-trien-1-al and a diluent or a carrier. 